Tracy Brown

F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma

F18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a powerful tool to investigate the role of tumor metabolic activity and its suppression by therapy for cancer survival. As part of Total Therapy 3 for newly diagnosed multiple myeloma, metastatic bone survey, magnetic resonance imaging, and FDG-PET scanning were evaluated in 239 untreated patients. All 3 imaging techniques showed correlations with prognostically relevant baseline parameters: the number of focal lesions (FLs), especially when FDG-avid by PET-computed tomography, was positively linked to high levels of beta-2-microglobulin, C-reactive protein, and lactate dehydrogenase; among gene expression profiling parameters, high-risk and proliferation-related parameters were positively and low-bone-disease molecular subtype inversely correlated with FL. The presence of more than 3 FDG-avid FLs, related to fundamental features of myeloma biology and genomics, was the leading independent parameter associated with inferior overall and event-free survival. Complete FDG suppression in FL before first transplantation conferred significantly better outcomes and was only opposed by gene expression profiling-defined high-risk status, which together accounted for approximately 50% of survival variability (R(2) test). Our results provide a rationale for testing the hypothesis that myeloma survival can be improved by altering treatment in patients in whom FDG suppression cannot be achieved after induction therapy.

Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3

Prognostic implications of 3 imaging tools, metastatic bone survey, magnetic resonance imaging, and positron emission tomography (PET), were evaluated in 2 consecutive Total Therapy 3 trials for newly diagnosed myeloma. Data including PET at baseline and on day 7 of induction as well as standard prognostic factors were available in 302 patients of whom 277 also had gene expression profiling (GEP)-derived risk information. According to multivariate analysis, more than 3 focal lesions on day 7 imparted inferior overall survival and progression-free survival, overall and in the subset with GEP-risk data. GEP high-risk designation retained independent significance for all 3 end points examined. Thus, the presence of > 3 focal lesions on day 7 PET follow-up may be exploited toward early therapy change, especially for the 15% of patients with GEP-defined high-risk disease with a median overall survival expectation of 2 years. This trial was registered at www.clinicaltrials.gov as #NCT00081939 and # NCT00572169.

Imaging of Multiple Myeloma and Related Plasma Cell Dyscrasias

Multiple myeloma (MM) is an incurable plasma cell malignancy of the bone marrow. MM has 3 components: diffuse marrow infiltration, focal bone lesions, and soft-tissue (extramedullary) disease. The hallmark biomarker in blood or urine is a monoclonal immunoglobulin, the monoclonal protein. Waldenstrom macroglobulinemia is a similar disease with secretion of IgM. Staging is classically performed with the 1975 Durie–Salmon system, which includes conventional radiographs. Recently updated, the Durie–Salmon Plus staging system includes CT, MRI, and 18F-FDG PET/CT. The hallmark radiographic lesion of symptomatic MM is a well-demarcated, focal osteolytic bone lesion. The number of focal bone lesions correlates inversely with outcome. Extramedullary disease is typically an aggressive, poorly differentiated form of MM that confers inferior outcome, with median survival of less than 1 y if present at diagnosis. Achievement of a complete response on 18F-FDG PET before stem-cell transplantation correlates with a superior outcome.

Standard and novel imaging methods for multiple myeloma: correlates with prognostic laboratory variables including gene expression profiling data

Multiple myeloma causes major morbidity resulting from osteolytic lesions that can be detected by metastatic bone surveys. Magnetic resonance imaging and positron emission tomography can detect bone marrow focal lesions long before development of osteolytic lesions. Using data from patients enrolled in Total Therapy 3 for newly diagnosed myeloma (n=303), we analyzed associations of these imaging techniques with baseline standard laboratory variables assessed before initiating treatment. Of 270 patients with complete imaging data, 245 also had gene expression profiling data. Osteolytic lesions detected on metastatic bone surveys correlated with focal lesions detected by magnetic resonance imaging and positron emission tomography, although, in two-way comparisons, focal lesion counts based on both magnetic resonance imaging and positron emission tomography tended to be greater than those based on metastatic bone survey. Higher numbers of focal lesions detected by magnetic resonance imaging and positron emission tomography were positively linked to high serum concentrations of C-reactive protein, gene-expression-profiling–defined high risk, and the proliferation molecular subgroup. Positron emission tomography focal lesion maximum standardized unit values were significantly correlated with gene-expression-profiling–defined high risk and higher numbers of focal lesions detected by positron emission tomography. Interestingly, four genes associated with high-risk disease (related to cell cycle and metabolism) were linked to counts of focal lesions detected by magnetic resonance imaging and positron emission tomography. Collectively, our results demonstrate significant associations of all three imaging techniques with tumor burden and, especially, disease aggressiveness captured by gene-expression-profiling–risk designation. (Clinicaltrials.gov identifier: NCT00081939)

The SNM Practice Guideline for Somatostatin Receptor Scintigraphy 2.0

VOICE Credit: This activity has been approved for 1.0 VOICE (Category A) credit. For CE credit, participants can access this activity on page 325 or on the SNM Web site (http://www.snm.org/ce_online) through December 31, 2013. You must answer 80% or the questions correctly to receive 1.0 CEH (Continuing Education Hour) credit.

Evaluation of dynamic [18F]-FDG-PET imaging for the detection of acute post-surgical bone infection.

Diagnosing bone infection in its acute early stage is of utmost clinical importance as the failure to do so results in a therapeutically recalcitrant chronic infection that can only be resolved with extensive surgical intervention, the end result often being a structurally unstable defect requiring reconstructive procedures. [18F]-FDG-PET has been extensively investigated for this purpose, but the results have been mixed in that, while highly sensitive, its specificity with respect to distinguishing between acute infection and sterile inflammatory processes, including normal recuperative post-surgical healing, is limited. This study investigated the possibility that alternative means of acquiring and analyzing FDG-PET data could be used to overcome this lack of specificity without an unacceptable loss of sensitivity. This was done in the context of an experimental rabbit model of post-surgical osteomyelitis with the objective of distinguishing between acute infection and sterile post-surgical inflammation. Imaging was done 7 and 14 days after surgery with continuous data acquisition for a 90-minute period after administration of tracer. Results were evaluated based on both single and dual time point data analysis. The results suggest that the diagnostic utility of FDG-PET is likely limited to well-defined clinical circumstances. We conclude that, in the complicated clinical context of acute post-surgical or post-traumatic infection, the diagnostic utility accuracy of FDG-PET is severely limited based on its focus on the increased glucose utilization that is generally characteristic of inflammatory processes.

Imaging of Multiple Myeloma, Solitary Plasmacytoma, MGUS, and Other Plasma Cell Dyscrasias

The significance of medical imaging in multiple myeloma was established in 1975 with the classic description of the Durie–Salmon staging system which incorporated the presence and number of focal osteolytic lesions in the staging scheme. A third of a century later, this staging system remains in use, though augmented by advances in medical imaging. By the early 1980s, CT imaging demonstrated more focal bone lesions than were seen with standard radiographs as well as extramedullary disease. By the 1980s, MRI imaging revealed skeletal disease that was not apparent by either standard x-rays or CT, focal plasmacytomas in bone that had not yet produced focal osteolysis, and diffuse marrow infiltration. Subsequent work throughout the 1990s developed and established MRI as a very powerful tool to demonstrate the full extent of skeletal disease with resolution approaching a few millimeters. MRI was also used to direct biopsies of focal lesions which increased the detection rate of clinically relevant information compared to random marrow biopsies. However, standard MRI lacked the wide field of view of CT and was both considerably more expensive and less widely available than CT. An additional weakness of standard x-rays, CT, and MRI was their limited utility in the demonstration of response to treatment. By the mid- to late 1990s, the utility of 18F-FDG PET and (after 2000) PET/CT was apparent. PET/CT was particularly powerful since it provided a “whole-body” examination combining the utility of CT (“anatomy”) with a “metabolic” image that was linked to the Warburg physiology of tumors, at a fraction of the cost of an extensive MRI. Thus, PET and PET/CT can demonstrate both active disease and, very importantly, response to treatment. The PET image fused to the CT portion of the PET/CT also provides a “free” whole-body metastatic bone survey that can reveal not only focal bone lesions but also additional clinically relevant findings (fractures or impending fractures, additional malignancies, occult infections, unsuspected regions of tumor involvement such as extramedullary tumor). Recent work has established the fundamental importance of 18F-FDG PET and PET/CT for the baseline evaluation of patients with multiple myeloma and related plasma cell dyscrasias, as well as for subsequent evaluations related to patient management. Future directions for imaging research in multiple myeloma will include PET imaging with isotopes other than 18F-FDG and whole-body MRI.

Pathophysiologic correlates of 82Rb biodistribution in cardiac PET/CT.

PurposePET perfusion imaging with 82Rb is a powerful tool for evaluating coronary artery disease (CAD). Little is known about normal patterns or significance of 82Rb lung distribution in the setting of heart disease. Herein, PET/CT hybrid imaging was used to obtain insights into the frequency and potential radiomorphologic correlates of altered 82Rb distribution.MethodsMyocardial perfusion PET/CT studies of 58 patients referred for workup of CAD were analyzed [28 normal and 30 patients with low left ventricular ejection fraction (LVEF)]. Organ regions of interest were placed on PET images, and 82Rb uptake was measured and compared under resting and stress conditions.ResultsQualitatively increased lung uptake was observed in 13 patients—5 with normal LVEFR and 8 with reduced LVEFR; 12 of 13 had lung infiltrates/atelectasis on CT. Lung to heart ratios in the normal and low EF groups were (mean ± SD) 0.168 ± 0.047 and 0.171 ± 0.075 at rest, and 0.128 ± 0.035 and 0.147 ± 0.067 during stress (p = 0.87 and 0.18, respectively). Lung to liver ratios were not significantly different between the two groups under stress or rest conditions.ConclusionIncreased lung uptake of 82Rb occurs in a subset of patients referred for workup of CAD by PET/CT and may be influenced by primary parenchymal abnormalities and LV dysfunction. Thus, the relevance of pulmonary 82Rb uptake as a marker of cardiac outcome may be limited. Larger studies are needed to determine how non-cardiac 82Rb uptake and CT findings may be integrated to increase the diagnostic and prognostic value of cardiac PET/CT.